Evaluation of the optimal duration of immunosuppressive treatment after induction of remission, in patients with ANCA vasculitis
| ISRCTN | ISRCTN13739474 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13739474 |
| Secondary identifying numbers | 1 |
- Submission date
- 04/01/2017
- Registration date
- 10/01/2017
- Last edited
- 30/05/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Vasculitis is a condition in which the immune system attacks blood vessels by mistake, leading them to lead fluid into tissues causing inflammation (swelling). This happens because antibodies, which are normally produced by the immune system to fight germs, start attacking a type of white blood cell called neutrophils. In the case of ANCA vasculitis, the antibodies which are attacking the neutrophils are called Anti-Neutrophil Cytoplasmic Autoantibodies (ANCA). When ANCAs attack the neutorphils, the neutrophils in turn start to attack the walls of small blood vessels in different parts of the body. The treatment of ANCA vasculitis is by drugs which suppress the immune system (immunosuppressive drugs). These drugs, which include steroids, have side-effects and it is desirable to reduce the doses and stop them where possible. However vasculitis can return when the drugs are reduced or stopped. The aim of this study is to investigate how long immunosuppressive drugs should be given to patients with vasculitis.
Who can participate?
Adults with ANCA vasculitis which has been treated and is now under good control.
What does the study involve?
Participants are randomly allocated to one of two groups. In both groups, before they are allocated to the different groups, participants are taking immunosuppressive therapy, which involves taking the drug azathioprine and prednisolone every day by mouth for three months. Those in the first group then stop taking the azathioprine and lower the dose of prednisolone, which is stopped altogether by five months later. Those in the second group continue to take their azathioprine until the end of the study (30 months) and gradually reduce and eventually stop taking their prednisolone between 18 and 24 months. At the start of the study and then every three months until the end of the study (30 months), participants attend visits where they have blood samples taken to find out whether the vasculitis has come back and to assess their health.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
1. Addenbrooke's Hospital (UK)
2. Hôpital Cochin (France)
3. Maastricht University (Netherlands)
4. Universitetssjukhuset Linköping (Sweden)
5. Uniklinikum Aachen (Germany)
6. Provicial Barcelona Hospital Hospital Clínic de Barcelona (Spain)
When is the study starting and how long is it expected to run for?
January 1994 to September 2012
Who is funding the study?
European Community (EC) BIOMED-1 Concerted Action Programme (UK)
Who is the main contact?
Prof. Alexandre Karras
alexandre.karras@aphp.fr
Contact information
Scientific
Hôpital Européen Georges-Pompidou
Nephrology Department
20 Rue Leblanc
Paris
75015
France
 ORCID ID |
0000-0002-3075-7739 |
|---|---|
| Phone | +33 (0)1 56 09 37 60 |
| alexandre.karras@aphp.fr |
Study information
| Study design | Prospective open-label randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Randomised controlled trial comparing relapse rate between standard (18 to 24 months) and prolonged (48 months) immunosuppression with azathioprine and prednisolone, in patients in the remission phase of ANCA vasculitis |
| Study acronym | REMAIN |
| Study objectives | Prolonged maintenance therapy with low-dose prednisolone and azathioprine reduces long-term morbidity in systemic vasculitis, by reducing the frequency of relapse, when compared with cessation of therapy in the second year, as suggested by current guidelines. |
| Ethics approval(s) | NHS Executive North West MREC, 07/03/2001, ref: MREC/00/8/74 |
| Health condition(s) or problem(s) studied | ANCA-associated vasculitis |
| Intervention | Patients with ANCA vasculitis in stable remission are included 18 to 24 months after initiation of immunosuppressive therapy. Patients are randomised in a 1:1 ratio to either withdraw from immunosupprssion (Group W) or continue immunosuppression (Group C). Prior to randomisation, immunosuppressive therapy involves oral azathioprine at a daily dose of 1 mg/kg and oral prednisolone at the dose of 7.5 mg/day. Group W: Participants receive oral azathioprine at the dose of 0.75 mg/kg for 3 months and then stop this drug. In addition, prednisolone is tapered to 5 mg/day at randomisation and then progressively stopped before month 5. Group C: Participants continue oral azathioprine at the daily dose of 1 mg/kg for 30 months, until end of study. In addition, oral prednisolone is tapered to 5 mg/day at month 3, and then continued until month 18. After month 18, prednisolone is progressively stopped, before reaching month 24. Duration of follow-up for both arms will be 30 months, with evaluation (examination and blood tests) every 3 months. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | 1. Azathioprine 2. Prednisolone |
| Primary outcome measure | Rate of vasculitis relapse is measured using the Birmingham Vasculitis Activity Score (BVAS) continuously from baseline to 30 months. |
| Secondary outcome measures | 1. Incidence of major and minor relapse is measured using the Birmingham Vasculitis Activity Score (BVAS) continuously from baseline to 30 months 2. Mortality rate is measured continuously from baseline to 30 months 3. Adverse events of therapy are observed continuously from baseline to 30 months 4. Cumulative damage is assessed using the Vasculitis Damage Index (VDI) from baseline to 30 months 5. Renal function is assessed by measuring estimated Glomerular Filtration Rate (eGFR) from baseline to 30 months 6. Incidence of end-stage renal disease (ESRD) is monitored from baseline to 30 months 7. ANCA status |
| Overall study start date | 01/01/1994 |
| Completion date | 01/09/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 116 |
| Key inclusion criteria | 1. Diagnosis of MPA, GPA or renal-limited vasculitis 2. Renal involvement and/or other threatened loss of function of a vital organ (lung, brain, eye, motor nerve, or gut); and ANCA positivity (ANCA-negative patients were eligible for enrollment in the study only when there was histologic confirmation of pauci-immune vasculitis) 3. Remission-induction therapy with cyclophosphamide and prednisolone for at least 3 months, with or without plasma exchanges 4. Stable remission on azathioprine/prednisolone 5. Aged 18 years and over |
| Key exclusion criteria | 1. Age under 18 years 2. Pregnancy 3. Previous malignancy 4. Known HIV infection 5. Previous life-threatening relapse 6. End-stage renal disease (ESRD) at inclusion and allergy to study medications. Patients not in stable remission for at least six months at 18 months after commencement of therapy and patients who had discontinued azathioprine and/or prednisolone are excluded from the study. |
| Date of first enrolment | 01/09/1998 |
| Date of final enrolment | 01/03/2010 |
Locations
Countries of recruitment
- Czech Republic
- England
- Finland
- France
- Germany
- Italy
- Lithuania
- Netherlands
- Spain
- Sweden
- Switzerland
- United Kingdom
Study participating centres
Hills Road
Cambridge
CB2 0QQ
United Kingdom
27 Rue du Faubourg Saint-Jacques
Paris
75014
France
Minderbroedersberg 4-6
Maastricht
6211 LK
Netherlands
Universitetssjukhuset
Linkoping
581 85
Sweden
Pauwelsstraße 30
Aachen
52074
Germany
Carrer de Villarroel, 170
Barcelona
08036
Spain
Sponsor information
Research organisation
Box 57
Department of Renal Medicine
Addenbrooke's Hospital
Cambridge
CB2 2QQ
United Kingdom
| Website | http://www.vasculitis.org/ |
|---|
Funders
Funder type
Research organisation
No information available
Results and Publications
| Intention to publish date | 31/12/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact reviewed journal. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Alexandre Karras (akarras3@gmail.com) or David Jayne (dj106@cam.ac.uk) |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/10/2017 | Yes | No |
Editorial Notes
30/05/2017: Publication reference added.
